An adopted Nuclear Receptor for Cancer and Metabolic Diseases
Liver receptor homologue 1 (LRH-1) modulates several physiological functions including: bile acid, lipid, and glucose metabolism as well as intestinal homeostasis through the regulation of key target genes.
Aberrant expression and activity of LRH-1 have been linked to multiple human diseases, highlighting this orphan nuclear receptor as an interesting therapeutic target for multiple pathologies.
Genetic ablation of LRH-1 leads to a strong block of cancer progression, supporting the idea that molecules capable of inhibiting LRH-1 functions can represent a new anti-cancer targeted-therapy.
We have developed first drug-like small molecule LRH-1 inverse agonist able to significantly slow down pancreatic cancer in animal model studies both as standalone therapy as well as in combination with FDA-approved chemotherapies.